ArticleMolecular therapy. Advances2026
Immune shielding of viral vectors via capsid engineering with genetically encoded zwitterionic peptides.
Article in Molecular therapy. Advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Pre-existing neutralizing antibodies (NAbs) and blood proteins can rapidly inactivate therapeutic viral vectors and trigger immune toxicities in patients. To overcome these challenges, we engineered the surfaces of adenovirus (Ad) by incorporating genetically encoded "protective shields" to reduce the recognition by host factors. AlphaFold3 modeling showed that inserting a structured biotin acceptor peptide (BAP) into hypervariable region 5 (HVR5) of the viral capsid protein hexon produced a rigid surface protrusion, whereas inserting a disordered, zwitterionic glutamic acid-lysine (EK) peptide formed a flexible canopy over the hexon. Although inserting EK peptides into the capsid impaired viral entry and intracellular trafficking that led to reduced viral transduction
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